rs778083552

Variant names:

• chr6-42923332-C-A
• NM_138296.3:c.364C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-42923332-C-A
• chr6-42923332-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138296.3(PTCRA):​c.364C>A​(p.Pro122Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P122S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PTCRA NM_138296.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85

Genes affected

PTCRA (HGNC:21290): (pre T cell antigen receptor alpha) The protein encoded by this gene is a single-pass type I membrane protein that is found in immmature but not mature T-cells. Along with TCRB and CD3 complex, the encoded protein forms the pre-T-cell receptor complex, which regulates early T-cell development. Four transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCRA	NM_138296.3	c.364C>A	p.Pro122Thr	missense_variant	Exon 2 of 4	ENST00000304672.6	NP_612153.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCRA	ENST00000304672.6	c.364C>A	p.Pro122Thr	missense_variant	Exon 2 of 4	1	NM_138296.3	ENSP00000304447.2
PTCRA	ENST00000441198.4	c.289C>A	p.Pro97Thr	missense_variant	Exon 3 of 5	1		ENSP00000409550.1
PTCRA	ENST00000446507.5	c.59-897C>A		intron_variant	Intron 1 of 2	1		ENSP00000392288.1
PTCRA	ENST00000616441.2	c.364C>A	p.Pro122Thr	missense_variant	Exon 2 of 4	2		ENSP00000477815.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461710 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727138

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T;.;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-7.4	D;D;.
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.53
MutPred		0.25		Gain of relative solvent accessibility (P = 0.0289);.;Gain of relative solvent accessibility (P = 0.0289);
MVP		0.81
MPC		0.66
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.90
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-42891070;